Author/Authors :
Diakos، نويسنده , , Nikolaos A. and Selzman، نويسنده , , Craig H. and Sachse، نويسنده , , Frank B. and Stehlik، نويسنده , , Josef and Kfoury، نويسنده , , Abdallah G. and Wever-Pinzon، نويسنده , , Omar and Catino، نويسنده , , Anna and Alharethi، نويسنده , , Rami and Reid، نويسنده , , Bruce B. and Miller، نويسنده , , Dylan V. and Salama، نويسنده , , Mohamed and Zaitsev، نويسنده , , Alexey V. and Shibayama، نويسنده , , Junko and Li، نويسنده , , Hui and Fang، نويسنده , , James C. and Li، نويسنده , , Dean Y. and Drakos، نويسنده , , Stavros G.، نويسنده ,
Abstract :
AbstractBackground
mal models of heterotopic transplantation, mechanical unloading of the normal, nonhypertrophic heart results in atrophy. Primarily on the basis of these animal data, the notion that chronic left ventricular assist device (LVAD)-induced unloading will result in atrophy has dominated the clinical heart failure field, and anti-atrophic drugs have been used to enhance the cardiac recovery potential observed in some LVAD patients. However, whether unloading-induced atrophy in experimental normal heart models applies to failing and hypertrophic myocardium in heart failure patients unloaded by continuous-flow LVADs has not been studied.
ives
udy examined whether mechanical unloading by continuous-flow LVAD leads to myocardial atrophy.
s
spectively examined myocardial tissue and hemodynamic and echocardiographic data from 44 LVAD patients and 18 untransplanted normal donors.
s
myocyte size (cross-sectional area) decreased after LVAD unloading from 1,238 ± 81 μm2 to 1,011 ± 68 μm2 (p = 0.001), but not beyond that of normal donor hearts (682 ± 56 μm2). Electron microscopy ultrastructural evaluation, cardiomyocyte glycogen content, and echocardiographic assessment of myocardial mass and left ventricular function also did not suggest myocardial atrophy. Consistent with these findings, t-tubule morphology, cytoplasmic penetration, and distance from the ryanodine receptor were not indicative of ongoing atrophic remodeling during LVAD unloading. Molecular analysis revealed no up-regulation of proatrophic genes and proteins of the ubiquitin proteasome system.
sions
ural, ultrastructural, microstructural, metabolic, molecular, and clinical functional data indicated that prolonged continuous-flow LVAD unloading does not induce hypertrophy regression to the point of atrophy and degeneration. These findings may be useful in designing future investigations that combine LVAD unloading and pharmaceutical therapies as a bridge to recovery of the failing heart.
